Relaxin is a product of the human corpus luteum of pregnancy and is present in maternal serum throughout pregnancy. Relaxin is also produced by human decidua and is found in human semen plasma. Relaxin stimulates sperm motility and sperm penetration in cervical mucus. The objectives of the proposal are to further understand the roles and control of human relaxin. Monoclonal antibodies to human relaxin have been produced utilizing partially purified human seminal relaxin as immunogen. These antibodies will be utilized to purify seminal relaxin by immunoaffinity chromatography, establish a homologous radioimmunoassay for human relaxin, and identify translation products of mRNA from male and female reproductive tract tissues. Relaxin will be localized immunohistochemically in both male and female reproductive tissues. The relationship of relaxin to abnormalities of pregnancy such as diabetes and incompetent cervix will be observed. Relaxin concentrations will be correlated with abnormalities of semen analysis. The stimuli for seminal relaxin secretion will be studied in vivo using hCG and testosterone. Determination of relaxin production in human decidua will be done. A potential relaxin deficiency syndrome will be defined. The effect of relaxin on human sperm motility will be further clarified using computer-assisted measurement. The effect of relaxin on sperm penetration of zona-free hamster eggs will be studied. Anti-human relaxin antibodies will be used to block sperm motility and the action of relaxin on sperm. The mechanism of action of relaxin on semen will be studied by observing the effect of relaxin on cAMP levels and calcium uptake. Relaxin receptors will be studied. These studies will provide greater understanding of major reproductive mechanisms involved in pregnancy maintenance and fertility. Many of these studies can be translated into useful therapies of male infertility and pregnancy loss.